Serum tau protein elevation in migraine: a cross-sectional case- control study

Background: Migraine is a disorder associated with neuropeptide release, pain and inflammation. Tau protein has recently been linked to inflammatory diseases and can be influenced by neuropeptides such as CGRP, a key neurotransmitter in migraine. Here, we report serum concentrations of total-tau protein in migraine patients and healthy controls. Methods: : In this cross-sectional study, interictal blood samples from n=92 patients with episodic migraine (EM), n=93 patients with chronic migraine (CM), and n=42 healthy matched controls (HC) were studied. We assessed serum total-tau protein (t-tau), and for comparison neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L (UCH-L1) concentrations using the Neurology 4-plex kit, on a single molecule array HD-X Analyzer (Quanterix Corp Lexington, MA). Matched serum/cerebrospinal fluid (CSF) samples were used for post-hoc evaluations of a central nervous source of relevant findings. We applied non-parametric tests to compare groups and assess correlations. Results: : Serum t-tau concentrations were elevated in EM [0.320 (0.204 to 0.466) pg/mL] and CM [0.304 (0.158 to 0.406) pg/mL] patients compared to HC [0.200 (0.114 to 0.288) pg/mL] (p=0.002 vs. EM; p=0.025 vs. CM). EM with aura [0.291 (0.184 to 0.486 pg/mL); p= 0.013] and EM without aura [0.332 (0.234 to 0.449) pg/mL; p=0.008] patients had higher t-tau levels than HC but did not differ between each other. Subgroup analysis of CM with/without preventive treatment revealed elevated t-tau levels versus HC only in the non-prevention group [0.322 (0.181 to 0.463) pg/mL; p=0.009]. T-tau was elevated in serum (p=0.028) but not cerebrospinal fluid (p=0.76). In contrast to t-tau, all proteins associated with cell damage (NfL, GFAP, and UCH-L1), did not differ between groups. Discussion: Migraine is associated with t-tau elevation in serum but not in the CSF. Our clinical study identifies t-tau as a new target for migraine research.